FDA's response wasn't what they expected: the agency had no established basis for believing that biomarker actually tracked with how patients felt or functioned day to day, and without that link, a clean p-value wasn't going to carry the program. The sponsor had generated rigorous evidence. It just wasn't evidence anyone downstream could act on. What followed was roughly 18 months retrofitting a patient-reported outcome measure into the confirmatory study a fix that would have cost a fraction of the time and money if someone had raised the question before the trial was designed around that endpoint in the first place.